Epidermolysis bullosa (EB) is a group of hereditary and acquired diseases of the skin and mucous membranes that share the common feature of the formation of blisters and erosions in response to minor trauma (Fine et al., 2000).
In humans, the clinical forms of hereditary EB are divided into three main categories, each typified by the level of skin separation within the dermal-epidermal basement membrane zone and by the proteins involved. EB simplex (EBS) is characterized by separation occurring in the basal keratinocytes due to mutations in the keratin 5 and 14 genes or in the hemidesmosomal component plectin (Fuchs, 1992). In dystrophic EB (DEB), the skin separates at the lower layer of the basement membrane zone, the lamina densa, as a result of defects in anchoring fibrils (Uitto and Christiano, 1993). In junctional EB (JEB), blister formation takes place within the lamina lucida of the dermal-epidermal basement membrane and several mutations have been described in the three genes (LAMA3, LAMB3, and LAMC2) that encode the anchoring filament protein, laminin 5, and the two transmembrane components of the hemidesmosome (HD), collagen XVII and integrin α6β4. Among the JEB variants, the non-Herlitz or mild forms of JEB (non-H JEB) are characterized by chronic and localized blistering with non-shortening of the patient's life span. Hemidesmosomes are present but usually reduced in number. Herlitz JEB (H-JEB) represents the most severe and the most frequent form of JEB (greater than 50% of cases). H-JEB is characterized by generalized blistering with erosions of the skin and mucous membranes, and is lethal in early childhood. Ultrastructural and immunohistochemical observations demonstrate abnormalities in hemidesmosome anchoring filaments complexes. Immunostaining of the skin of patients affected by H-JEB reveals absence of laminin-5.
Laminin 5 is synthesized within the basal epithelial cells as a heterotrimeric molecule composed of an α3 (200 kDa), a β3 (140 kDa) and a γ2 (155 kDa) chain that associate to form a triple-stranded α-helical coiled-coil rod domain (Engel, 1991). A large number of distinct mutations (greater than 100) have been identified in the three genes encoding the polypeptide subunits of laminin 5 (Pulkkinen and Uitto, 1999).
Animal models for mechanobullous disorders have been described in the literature, including transgenic mouse models and xenograft models but naturally-occurring, well-characterized animal models are rare.
Clinical reports of sporadic cases of hereditary EB have been described in a range of animals including sheep (Bruckner-Tuderman), cattle, cats, dogs and horses, but electron microscopy examination was often absent, the breeding history of animals incomplete and the inheritance mode of the disease unclear. Clinical features observed in humans often differ in animals and this is probably due to differences in the skin characteristics among species.
In order to understand the molecular basis of this disease in horses, with a view to minimizing its occurrence, it would be desirable to clone the relevant genes in an attempt to determine the cause of one or more forms of EB in horses.